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Archive > Volume 23 Issue 2 > 2016,23(2):195-200. DOI:10.3872/j.issn.1007-385X.2016.02.007 Prev Next
Basic Research
Arsenic trioxide negatively regulating tumor immune suppression function of myeloid-derived suppressor cells
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Abstract:
Objective:To explore whether arsenic trioxide (As2O3) negatively regulate function of tumor immune tolerance induced with inhibiting myeloid-derived suppressor cells (MDSCs) through inhibition of the MDSCs. Methods: Melanoma B16 cells and liver cancer H22 cells were subcutaneously injected into the C57BL/6 mice respectively to construct xenograft models. Growth of the xenografts was observed after treatment with As2O3. Immunophenotypes of MDSCs and other immune cells in spleen tissues of the mice with the xenograft, and effect of As2O3 (2 μmol/L) on the differentiation of MDSCs in the mouse models with B16 cells were detected by flow cytometry assay. the mouse models with B16 cells were randomly divided into two groups, namely As2O3 treatment group and control group. Changes of immunosuppressive activity of T cell mediated by MDSCs were detected with mixed lymphocytes reaction. Concentrations of TNF-α and IL-10 in serum of the mouse model with B16 cells and supernatant of MDSCs cultures were detected by ELISA. Results: As2O3 could inhibit growth of the xenografts in the mouse models with B16 and H22 cells, prolong survival periods of the mouse models with B16 cells, and significantly decrease percentages of MDSCs in spleen of the mouse models. After treatment with As2O3 (2 μmol/L ) in vitro for 5 d, the proportion of mature DCs (CD11c+/CD40+) in MDSCs of the mouse models with B16 cells was significantly higher than that of mice in control group (\[27.38±4.57\]% vs \[17.44±4.51\]%，P=0.0078). The immunosuppressive activity of MDSCs against T cells in the As2O3 treatment group was significantly lower than that in the control group (P=0.016), and the concentrations of TNF-α and IL-10 in mouse serum of As2O3 treatment group and supernatant of MDSCs cultures were significantly lower than that of the control group. Conclusion: As2O3 could induce maturation of MDSCs, down regulate its immunosuppressive activity and negatively regulate tumor suppression function of MDSCs.
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Project Supported:
Project supported by the Natural Science Foundation of Science and Technology Committee of Shanghai(No.13ZR1405000）
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